INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH … 1289.pdf · Research Article CODEN: IJPRNK ... Ingredient Aurobindo Pharma Ltd; Hyderabad. 2. ... Pharma Glidant Meruchem

Research Article CODEN: IJPRNK Impact Factor: 5.567 ISSN: 2277-8713 M. Chandrakanth, IJPRBS, 2016; Volume 5(4): 149-165 IJPRBS

Available Online at www.ijprbs.com 149

FORMULATION AND EVALUATION OF FUDOSTEINE FILM COATED IMMEDIATE

RELEASE TABLETS

M. CHANDRAKANTH, P. PREM KUMAR, MANOHAR BABU S

Department of Pharmaceutics, SIMS College of Pharmacy, SIMS Group of Institutions, Mangaldas Nagar, Guntur,-522001, Andhra Pradesh,

India.

Accepted Date: 16/08/2016; Published Date: 27/08/2016

Abstract: The selected method yielded uniform and reproducible film coated tablets of

Fudosteine with the given excipients. The hardness, friability, weight variation, drug content,

and in vitro release were uniform and reproducible. The release was inversely proportional to

the binder concentration irrespective of the polymer used. The dissolution profile of the

formulation F10 was found to have equivalent percentage drug release with that of the

innovator product. Selected Fudosteine tablets were found to be stable with respect to drug

content, drug release, friability, weight variation, hardness and thickness. FTIR studies revealed

no chemical interaction and indicating stability of drug in tablets. Hence, Fudosteine tablets

containing mannitol (diluent), Povidone K-30 (binder), croscaramellose sodium (disintegrant),

Colloidal Silicon Dioxide (glidant), Magnesium Stearate (Lubricant) and Opadry – AMB (coating

Material) showed promising results and there exist a scope for in vivo evaluation using

suitable animal models.

Keywords: Povidone K-30 (binder), croscaramellose sodium (disintegrant), Colloidal Silicon

Dioxide (glidant), Magnesium Stearate (Lubricant)

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M. Chandrakanth, IJPRBS, 2016; Volume 5(4): 149-165



INTRODUCTION

Dosage forms are also referred to as “Drug Delivery Systems” or “Finished Drug Products”. A

drug delivery system (DDS) is defined as a formulation or a device that enables the introduction

of a therapeutic substance into the body and improves its efficacy and safety by controlling the

rate, time, and site of release of drugs in the body. The goal of any drug delivery system is to

provide a therapeutic amount of drug in the proper site in the body to achieve promptly and

then to maintain the desired drug concentration1, 2. That is, the drug delivery system should

deliver drug at a rate dedicated by the needs of the body over a specified period of treatment.

Oral route of drug administration is most appealing route for delivery of drugs for various

dosage forms. The tablet is one of the most preferred dosage forms, because of its ease of

administration, accurate dosing and stability as compared to oral liquid dosage forms. Tablets

may be defined as solid unit pharmaceutical dosage forms containing drug substance with or

without suitable excipients and prepared by either compression or molding methods3, 4.

The first step in the development of dosage form is preformulation, which can be defined as

investigation of physiochemical properties of drug substances alone and when combined with

excipients. The main objective of preformulation studies, is to develop stable and bioavailable

dosage form and study of factors affecting such as stability, bioavailability and to optimize so as

to formulate the best dosage form. Here, optimization of formulation means finding the best

possible composition. Compressed tablets are formed by applying pressure, for which

compression machines (tablet presses) are used and they are made from powdered crystalline

or granular material, alone or in combination with binder, disintegrants, release polymers,

lubricants and diluents and in some cases with colorant5-10.

MATERIALS AND EQUPIMENTS USED

Table.1- List of materials used

S No Name of the product Grade Function Name of the supplier

1. Fudosteine - Active Pharmaceutical Ingredient

Aurobindo Pharma Ltd; Hyderabad.

2. Micro crystalline cellulose USP-NF (Avicel Ph 101)

Avicel Ph 101 Diluent FMC biopolymer

3 Povidone K-30 Kollidon 30 Binder BASF, Germany

4 Sodium starch glycolate Primogel Disintegrant FMC biopolymer



Table.2- List of Equipments used

Table.3-List of Components used in the Formulation

S.No Components Function

1 Mannitol – 35 Diluent

2. Povidone K-30 Binder

3 Iso-propyl alcohol Granulating Fluid

4 Cross Caramellose Sodium Disintegrant

5 Aerosil Glidant

6 Magnesium Stearate Lubricant

5 Colloidal silicon dioxide Aerosil 200 Pharma

Glidant Meruchem

6 Magnesium Stearate USP-NF

- Lubricant Ligamade

7 Opadry White - Film Coating Agent Colorcon

8 Opadry AMB - Film Coating Agnet Colorcon

S. No. Equipment Manufacturer Model no

1 Electronic Balance Sartorius AG GP3202

2 Sieves Scientific Engineering corporation Ltd.

ASL00

3 Blender RIMEK(KALWEKA) HD-410AC

4 Rapid Dryer Retsch TG-100

5 Co-Mill(COMIL) Rpm: 1000-6500

Quadro(220 Volts) U5-0280

6 Compression 16 Station

Cadmach SS00001

7 Compression 20 Station

Cadmach PR/SD/COMO1

8 Dissolution test apparatus Electro lab USP XXII TDT-08L

9 Stability chambers Thermo labs Standard

10 Coating Machine Gansons GAC-250

11 Hardness tester Tanco labs T3

12 Friabilator Electro Lab EF2

13 Mixer Philips HL1628

14 Sieve Shaker Retsch AS200digit

15 Bulk Density Apparatus Electro Lab ETD-1020

16 Fluid Bed Processor Pam-Glatt FP-01

17 Stirrer REMI-Motors RQT-124A



7 Opadry White Coating Material

8 Opadry AMB Coating Material

9 Purified Water Vehicle

RESULTS AND DISCUSSIONS

Table.4- List of Formulation Trials

Prototype Formulations

Ingredients(mg) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10

Fudosteine 200 200 200 200 200 200 200 200 200 200

Mannitol 35 21 21 19.5 15.5 13 11 11 8.5 6.5 6.5

Granulation

Povidone K-30 - - 4 4 4 4 5 5 4.5 4.5

Iso-propyl alcohol - Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S

Extra-Granular

Ac-Di-Sol 4 4 4 4 4 4 4 6.5 9 9

Talc - - 1.5 - - - - - -

Aerosil - - - 1.5 2.5 2.5 2.5 2.5 2.5 2.5

Magnesium Stearate

- - - - 1.5 2.5 2.5 2.5 2.5 2.5

Core Tablet Wt. 225 225 225 225 225 224 225 225 225 225

Coating

Opadry White - 6.75 6.75 6.75 6.75 6.75 6.75 - - -

Opadry AMB - - - - - - - 6.75 6.75 6.75

Coated Tablet Wt. 231.75 231.75 231.75 231.75 231.75 231.75 231.75 231.75 231.75

Table.5-Flow Properties of A.P.I

S. No Bulk Density (gm/ml)

Tap Density (gm/ml)

Compressibility Index Hausner’s Ratio

1 0.215 0.389 44.706 1.808

2 0.215 0.389 44.706 1.808

3 0.215 0.389 44.706 1.808

4 0.215 0.389 44.706 1.808

Table.6--Standard curve of Fudosteine in water at λmax 279nm

Concentration (µg/ml) Absorbance (279nm)

0 0

1 0.109



2 0.204

3 0.317

4 0.412

5 0.537

6 0.627

7 0.747

Fig: 1. Standard calibration curve of Fudosteine

Table.7- showing the solubility of Fudosteine (API) in various solvents.

Solvents Solubility

Water Freely Soluble

Formic Acid Very Soluble

Acetic Acid Slightly Soluble

Ethanol Very Slightly soluble

Diethyl Ether Insoluble

Table.8-Data of average Hardness for all the formulations of Fudosteine

Formulation Average Hardness (Kp)

F1 12±0.09

F2 8± 0.05

F3 11.5 ± 0.32

Concentration (µg/ml)



Table.9- Data showing the thickness for all formulations of Fudosteine

Formulation Thickness (mm)

F1 3.8-4.1

F2 4.1-4.2

F3 3.7-4.1

F4 4.0-4.1

F5 3.8-4.2

F6 3.9-4.1

F7 3.7-3.9

F8 4.0-4.2

F9 3.9-4.2

F10 3.9-4.2

Table.10- Data showing the results of Friability for all the formulations of Fudosteine

Formulation Percentage of weight loss (%)

F1 1.02±1.27

F2 0.05±0.01

F3 0.04±0.11

F4 0.028±0.02

F5 0.019±0.05

F6 0.013±0.06

F7 0.03±0.05

F8 0.04±0.012

F9 0.02±0.02

F10 0.012±0.03

F4 13± 0.12

F5 12± 0.08

F6 10.5± 0.33

F7 12 ± 0.25

F8 10.5 ± 0.12

F9 11 ± 0.13

F10 10± 0.15



Table.11- Data of average weight of tablets for all the formulation of Fudosteine

Formulation Average Weight (mg)

F1 210-237

F2 215-235

F3 215-234

F4 213-233

F5 216-229

F6 213-232

F7 214-234

F8 213-232

F9 215-236

F10 218-230

Table.12-Data of time for disintegration for all formulations of Fudosteine (n=6)

Formulation Disintegration time (minutes)

F1 6.0-6.5

F2 6.0-6.5

F3 8.0-8.5

F4 7.5-8.0

F5 7.5-8.0

F6 7.5-8.0

F7 7.0-7.5

F8 7.0

F9 6.5-7.0

F10 6.5-7.0

Table.13- Blend Flow Properties of Fudosteine Film Coated Tablets

Formulation Code

Bulk Density (gm/cc)

Tap Density (gm/cc)

Compressibility Index

Hausner’s Ratio

F1 0.436 0.577 24.44 1.32

F2 0.432 0.572 24.48 1.32

F3 0.436 0.577 24.44 1.32

F4 0.417 0.498 16.27 1.19

F5 0.399 0.6 33.50 1.50

F6 0.498 0.581 14.29 1.17

F7 0.379 0.498 23.90 1.31

F8 0.417 0.612 31.86 1.47



F9 0.498 0.64 22.19 1.29

F10* 0.379 0.489 22.49 1.29

Table.14- Physical Characteristics of Fudosteine Film Coated Tablets

Formulation code

Weight (mg/Tab)

Hardness (kg/cm2)

Thickness (mm)

Labelled Drug Content (mg)

% drug content

% Friability

F1 210-237 12±0.09 3.8-4.1 200 99.6 1.02±1.27

F2 215-235 8± 0.05 4.1-4.2 200 99 0.05±0.01

F3 215-234 11.5 ± 0.32 3.7-4.1 200 99.8 0.04±0.11

F4 213-233 13± 0.12 4.0-4.1 200 100.6 0.028±0.02

F5 216-229 12± 0.08 3.8-4.2 200 99.8 0.019±0.05

F6 213-232 10.5± 0.33 3.9-4.1 200 101 0.013±0.06

F7 214-234 12 ± 0.25 3.7-3.9 200 100 0.03±0.05

F8 213-232 10.5 ± 0.12 4.0-4.2 200 99.6 0.04±0.012

F9 215-236 11 ± 0.13 3.9-4.2 200 99.2 0.02±0.02

F10* 218-230 10± 0.15 3.9-4.2 200 99.89 0.012±0.03

Table.15-Dissolution profiles of all Formulations

Time (h) Cumulative % drug dissolved

F1 F2 F3 F4 F5 F6 F7 F8 F9 F10*

5 54.2 55.5 48.8 53.4 49.2 51.6 43.5 51.2 42.2 58.8

10 86.4 82.1 83.2 82.1 80.6 81.5 70.6 81.6 70.5 87

15 99.2 97.4 98.7 96.8 94.6 95.5 87.3 95.1 86.8 98.6

20 100.7 100.2 100.6 99.8 97.9 98.6 97.1 100.2 96.2 100.2

30 100.9 99.9 100.7 100.3 100.01 100.5 100.8 100.4 101.5 100.4

Fig-2: First Order plot for F9

y = -0.0779x + 2.206R² = 0.9788

-1

0

1

2

0 10 20 30 40

log

cum

ula

tive

%

un

dis

solv

ed

Time (Minutes)

First order plot for F9

log cumulative %undissolved

Linear (logcumulative %undissolved)



Fig-3: Zero Order plot for F10

Fig-4: First Order plot for F10

Table.16- Dissolution profiles of all 10 formulations with innovator

Time F1 F2 F3 F4 F5 F6 F7 F8 F9 F10* innovator

0 0 0 0 0 0 0 0 0 0 0 0

5 54.2 55.5 48.8 53.4 49.2 51.6 43.5 51.2 42.2 58.8 58.8

10 86.4 82.1 83.2 82.1 80.6 81.5 70.6 81.6 70.5 87 87.8

15 99.2 97.4 98.7 96.8 94.6 95.5 87.3 95.1 86.8 98.6 99.2

20 100.7 100.2 100.6 99.8 97.9 98.6 97.1 100.2 96.2 100.2 100.9

30 100.9 99.9 100.7 100.3 100.01 100.5 100.8 100.4 101.5 100.4 101.4

y = -1.4568x + 34.308R² = 0.6214

-20

0

20

40

60

0 10 20 30 40

cum

ula

tive

% u

nd

isso

lve

d

Time (Minutes)

Zero order plot for F10

Cumulative %undissolved

Linear (Cumulative% undissolved)

y = -0.1468x + 2.4257R² = 0.9675

-3

-2

-1

0

1

2

0 10 20 30 40

log

cum

ula

tive

%

un

dis

solv

ed

Time (Minutes)

First order plot for F10

log cumulative %undissolved

Linear (log cumulative% undissolved)



Fig: 5. Dissolution profiles of F1 – F5 formulations with innovator

Fig: 6.Dissolution profiles of F6 – F10 formulations with innovator

Table.17-Innovator Product Dissolution Profile

Time (min) Innovator dissolution

0 58.8

5 87.8

10 99.2

15 100.9

20 101.4

30 58.8

0

20

40

60

80

100

120

0 10 20 30 40

Cu

mu

lati

ve %

Dru

g D

isso

lve

d

Time (h)

F1

F2

F3

F4

F5

Innovator

0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

F6

F7

F8

F9

F10

Innovator



Fig: 7.Dissolution profile of innovator product

Table.18- Comparison of Innovator Product ‘Vs’ Best Formulation

Time (Mins) Innovator F10

0 0 0

5 58.8 58.8

10 87 87.8

15 98.6 99.2

20 100.2 100.9

30 100.4 101.4

0

20

40

60

80

100

120

0 10 20 30 40

Cu

mu

lati

ve %

Dru

g D

isso

lve

d

Time (H)

Innovator Dissolution Profile

Cumulative % DrugDissolved



Fig: 8.Dissolution profile of best formulation with innovator

Fig- 9: FTIR of Pure drug Fudosteine

0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

Cu

mu

lati

ve %

Dru

g D

isso

lve

d

Time (H)

Dissolution of Innovator Vs Best Formulation

F10

Innovator



Fig- 10: FTIR of Fudosteine + Povidone k-30

Fig- 11: FTIR of Fudosteine + Cross Carmellose Sodium



Fig- 12: FTIR of Optimised Formulation (F10)

Table.19-Data showing various physico-chemical parameters after stability study

Conditions Parameter Initial data Data after one month

Long term storage conditions

Hardness (kp) 10± 0.15 10± 0.15


Friability (%) 0.012±0.03 0.012±0.03


Assay (%) 101.2 99.82

Intermediate Hardness (kp) 10± 0.15 10± 0.15

Intermediate Friability (%) 0.012±0.03 0.012±0.03

Intermediate Assay (%) 101.2 99.37

Accelerated Hardness (kg/cm2) 10± 0.15 10± 0.15

Accelerated Friability (%) 0.012±0.03 0.012±0.03



Accelerated Assay (%) 101.2 99.16

Table.20-Accelerated Stability Data for 1 Month

Condition Initial 40°C / 75% RH - 1 Month

HDPE HDPE - 1g Silica

PVC in TLP

PVDC in TLP

Description

Assay (%) 98.30 98.85 99.53 98.93 99.15

Water content (%) 0.74 0.84 0.78 0.63 0.79

Related substance (%)

Fudosteine sulfoxide 0.03 0.04 0.04 0.04 0.03

Cystine 0.04 0.04 0.04 0.04 0.04

Cysteine 0.00 0.00 0.00 0.00 0.00

N-Propanol Fudosteine 0.00 0.00 0.00 0.00 0.00

Bis Fudosteine 0.02 0.02 0.02 0.01 0.02

Fudosteine Disulfide 0.02 0.02 0.02 0.02 0.02

Fudosteine Ether 0.01 0.03 0.02 0.02 0.02

O-Acetyl Fudosteine 0.01 0.01 0.00 0.00 0.00

Unknown Impurity 0.02 0.02 0.01 0.00 0.00

Total Impurity 0.13 0.16 0.14 0.13 0.13

Table.21-Accelerated Stability data for 3 Months

Condition Initial 40°C / 75% RH - 3 Month

HDPE HDPE - 1g Silica

PVC in TLP PVDC in TLP

Description

Assay (%) 98.30 98.63 98.55 99.33 98.73

Water content (%) 0.74 1.42 1.39 1.34 1.45

Related substance (%)

Fudosteine sulfoxide 0.03 0.02 0.02 0.03 0.04

Cystine 0.04 0.03 0.03 0.03 0.03

Cysteine 0.00 0.00 0.00 0.00 0.00

N-Propanol Fudosteine 0.00 0.03 0.02 0.02 0.03

Bis Fudosteine 0.02 0.00 0.00 0.00 0.00

Fudosteine Disulfide 0.02 0.02 0.01 0.02 0.02

Fudosteine Ether 0.01 0.03 0.03 0.03 0.02

O-Acetyl Fudosteine 0.01 0.00 0.00 0.00 0.00

Unknown Impurity 0.02 0.00 0.00 0.00 0.00



Total Impurity 0.13 0.13 0.12 0.14 0.15

CONCLUSION

The selected method yielded uniform and reproducible film coated tablets of Fudosteine with

the given excipients. The hardness, friability, weight variation, drug content, and in vitro release

were uniform and reproducible. The release was inversely proportional to the binder

concentration irrespective of the polymer used. The release profile of fudosteine tablets

containing 4.5mg binder, binder quantity 25% and kneading time is 2.5 min was better among

all the trials. The mechanism of drug release was found to be Erosion of tablet. The dissolution

profile of the formulation F10 was found to have equivalent percentage drug release with that

of the innovator product. Selected Fudosteine tablets were found to be stable with respect to

drug content, drug release, friability, weight variation, hardness and thickness. FTIR studies

revealed no chemical interaction and indicating stability of drug in tablets. Hence, Fudosteine

tablets containing mannitol (diluent), Povidone K-30 (binder), croscaramellose sodium

(disintegrant), Colloidal Silicon Dioxide (glidant), Magnesium Stearate (Lubricant) and Opadry –

AMB (coating Material) showed promising results and there exist a scope for in vivo evaluation

using suitable animal models. The formulation F10 and process can be easily scaled up and can

be easily employed in large scale production because the process is simple, cost effective and

precise and also yields reproducible good tablets.

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3. Banker GS, Modern pharmaceutics, 3rd edition, Marcel Dekker Inc, Newyork, 2002,576 – 820.

4. Bi YX., Sunada, H., 25th edition, “Evaluation of rapidly disintegrating tablets prepared by

Direct compression method”, Drug DevInd PHarm., 1999, 571-581.

5. Chen, GL., Kuo MK., 52nd edition, “Formulation Design for Pioglitazone Rapid Release Tablet”,

Chinese pharmaceutical Journal, 2000, 295-300.

6. Chaudhari, PD., 42nd edition, “Formulation and evaluation of fast dissolving tablets of

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7. Herbert A, Lieberman, Leon lachman and JosepH B.Schwartz, Pharmaceutical Dosage Forms

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INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH … 1289.pdf · Research Article CODEN: IJPRNK ... Ingredient Aurobindo Pharma Ltd; Hyderabad. 2. ... Pharma Glidant Meruchem